The objective of the Structural Biology (StructBiol) Core of the Center to Develop Therapeutic Countermeasures to High-threat bacterial Agents is to provide a unique platform for Center investigators to engage in structure-based lead optimization projects by determining the x-ray crystallographic structures of antibacterial agents bound to target protein. The StructBiol Core will help investigators realize the enormous potential of detailed structural Information on ligand-protein interactions for target validation and lead optimization, thereby speeding the antibiotic discovery process. The specific aims of the StructBiol Core are: Aim 1: To provide services for all stages of structural analysis projects from protein expression and purification, biophysical characterization of ligand-target interactions, crystallization and structure determination to structure analysis and presentation. Aim 2: To use knowledge gained from structural studies ofthe inhibitor-target protein interactions to increase the binding affinity of lead compounds toward target and improve their pharmacological and chemical properties.